Peptides useful in vaccination against enteroviruses

Abstract

A synthetic peptide, suitable for use in vaccination against or diagnosis of a disease caused by an enterovirus and especially by a poliovirus, is the peptide coded for by codons 286-290 in the RNA sequence coding for the structural capsid protein VP1 of poliovirus type 3 Sabin strain or by equivalent codons of another enterovirus or is an antigenic equivalent thereof, the numbers of the codons being counted from the 5'-terminus of the nucleotide sequence coding for the VP1 capsid protein.

We claim: 
     
       1. A synthetic peptide, suitable for use in vaccination against or diagnosis of a disease caused by an enterovirus, which is a peptide coded for by codons 286 to 288 in the RNA sequence coding for the structural capsid protein VP1 of poliovirus type 3 Sabin strain or by equivalent codons of another enterovirus or is an antogenic equivalent of such a peptide, the antigenic equivalent being: (i) a said peptide modified by the inclusion therein of one or more changes to the amino acid sequence;   (ii) a first longer peptide which incorporates the sequence of a said peptide or a said modified peptide and which has up to four extra amino acid residues attached to the C-terminal end of the said sequence or up to four extra amino acid residues attached to the N-terminal end of said sequence or up to four extra amino acid residues attached to the C-terminal end and up to four extra amino acid residues attached to the N-terminal end of said sequence;   (iii) a second longer peptide which incorporates the sequence of a said peptide, a said modified peptide or a said first longer peptide, to which sequence is linked directly, by means of a further amino acid residue or by means of a disulphide bridge between Cys residues attached to each sequence of up to eighteen amino acid residues which comprises a hexapeptide sequence coded for by codons 93 to 98 in said RNA sequence or by equivalent codons of another enterovirus; or   (iv) a third longer peptide which incorporates the sequence of a said peptide, a said modified peptide or a said first longer peptide, to which sequence is linked directly, by means of a further amino acid residue or by means of a disulphide bridge between Cys residues attached to each sequence, a sequence comprising residues 58 and 59 of the VP3 capsid protein of an enterovirus of the same type but starting with a residue numbered no lower than 53 and ending with a residue numbered no higher than 68;   each said antigenic equivalent being capable of raising antobodies capable of neutralizing the same strain and type of enterovirus as said peptide to which said antigenic equivalent corresponds and the numbers of the codons being counted from the 5'-terminus of the nucleotide sequence for the VP1 capsid protein.   
     
     
       2. The peptide of claim 1, suitable for use in vaccination against or diagnosis of a disease caused by type 3 poliovirus, which comprises the sequence:   A.sub.0 -A.sub.1 -A.sub.2                                  (I)     in which A 0  is Arg or Lys and each A 1  and A 2  is independently Asn or Gln or A 0  is Arg and each of A 1  and A 2  is independently Asp or Glu.   
     
     
       3. The peptide of claim 2, wherein A 0  is Arg, A 1  is Asn and A 2  is Asn. 
     
     
       4. The peptide of claim 3, which comprises the sequence:   Gly-Val-Asp-Tyr-Arg-Asn-Asn-Leu-Asp-Pro-Leu.     
     
     
       5. The peptide of claim 1, suitable for use in vaccination against or diagnosis of a disease caused by type 2 poliovirus, which comprises the sequence:   Lys-A'.sub.1 -Gly     in which A' 1  is Asp or Glu.   
     
     
       6. The peptide of claim 5, which comprises the sequence:   Gly-Val-Asp-Tyr-Lys-Asp-Gly-Leu-Thr-Pro-Leu.     
     
     
       7. The peptide of claim 1, suitable for use in vaccination against or diagnosis of a disease caused by type 1 poliovirus, which comprises the sequence:   Lys-A.sub.4 -Gly-A.sub.5                                   (III)     in which A 4  is Asp or Glu and A 5  is Ser or Thr.   
     
     
       8. The peptide of claim 7, in which A 4  is Asp and A 5  is Thr. 
     
     
       9. The peptide of claim 8, which comprises the sequence:   Gly-Val-Asp-Tyr-Lys-Asp-Gly-Thr-Leu-Thr-Pro-Leu.     
     
     
       10. The peptide of claim 1, which further has a Cys residue at one or both ends. 
     
     
       11. A synthetic peptide, suitable for use in vaccination against or diagnosis of a disease caused by an enterovirus, which is a peptide coded for by codons 286 to 290 in the RNA sequence coding for the structural capsid protein VPI of poliovirus type 3 Sabin strain or by equivalent codons of another enterovirus or is an antigenic equivalent of such a peptide, the antigenic equivalent being: (i) a said peptide modified by the inclusion therein of one or more changes to the amino acid sequence,   (ii) a first longer peptide which incorporates the sequence of a said peptide or a said modified peptide and which has up to four extra amino acid residues attached to the C-terminal end of said sequence or up to four extra acid residues attached to the N-terminal end of said sequence or up to four amino acid residues attached to the C-terminal end and up to four extra amino acid residues attached to the N-terminal end of said sequence;   (iii) a second longer peptide which incorporates the sequence of a said peptide, a said modified peptide or a said first longer peptide, to which sequence is linked directly, by means of a further amino acid residue or by means of a disulphide bridge between Cys residues attached to each sequence, a sequence of up to eighteen amino acid residues which comprises a hexapeptide sequence coded for by codons 93 to 98 in said RNA sequence or by equivalent codons of another enterovirus; or   (iv) a third longer peptide which incorporates the sequence of a said peptide, a said modified peptide or a said first longer peptide, to which sequence is linked directly, by means of a further amino acid residue or by means of a disulphide bridge between Cys residues attached to each sequence, a sequence comprising residues 58 and 59 of the VP3 capsid protein of an enterovirus of the same type but starting with a residue numbered no lower than 53 and ending with a residue numbered no higher than 68;   each said antigenic equivalent being capable of raising antobodies capable of neutralizing the same strain and type of enterovirus as said peptide to which said antogenic equivalent corresponds and the numbers of the codons being counted from the 5'-terminus of the nucleotide sequence coding for the VP1 capsid protein.   
     
     
       12. The peptide of claim 11, suitable for use in vaccination against or diagnosis of a disease caused by type 3 poliovirus, which comprises the sequence:   A.sub.0 -A.sub.1 -A.sub.2 -Leu-A.sub.3                     (I)     in which (i) A 0  is Arg, each of A 1  and A 2  is independently Asn or Gln and A 3  is Asp or Glu or (ii), with the others of A 0  to A 3  being defined under (i), A 0  is Arg or A 1  or A 2  is Asp or Glu.   
     
     
       13. The peptide of claim 12, wherein A 0  is Arg, A 1  is Asn, A 2  is Asn and A 3  is Asp. 
     
     
       14. The peptide of claim 13, which comprises the sequence:   Gly-Val-Asp-Tyr-Arg-Asn-Asn-Leu-Asp-Pro-Leu.     
     
     
       15. The peptide of claim 11, suitable for use in vaccination or diagnosis of a disease caused by type 2 poliovirus, which comprises the sequence:   Lys-A'.sub.1 -Gly-Leu-A'.sub.3     in which A' 1  is Asp or Glu and A' 3  is Thr or Ser.   
     
     
       16. The peptide of claim 15, which comprises the sequence:   Gly-Val-Asp-Tyr-Lys-Asp-Gly-Leu-Thr-Pro-Leu.     
     
     
       17. The peptide of claim 11, suitable for use in vaccination against or diagnosis of a disease caused by type 1 poliovirus, which comprises the sequence:   Lys-A.sub.4 -Gly-A.sub.5 -Leu-A.sub.6                      (III)     in which A 4  is Asp or Glu and each of A 5  and A 6  is independently Ser or Thr.   
     
     
       18. The peptide of claim 17, in which A 4  is Asp and A 5  and A 6  are both Thr. 
     
     
       19. The peptide of claim 18, which comprises the sequence:   Gly-Val-Asp-Tyr-Lys-Asp-Gly-Thr-Leu-Thr-Pro-Leu.     
     
     
       20. The peptide of claim 11, which further has a Cys residue at one or both ends. 
     
     
       21. A synthetic peptide, suitable for use in vaccination against or diagnosis of a disease caused by a poliovirus, which is a peptide coded for by codons 286 to 288 in the RNA sequence coding for the structural capsid protein VP1 of poliovirus type 3 Sabin strain or by equivalent codons of another poliovirus or is an antigenic equivalent of such a peptide, the antigenic equivalent being: (i) a said peptide modified by the inclusion therein of one or more changes to the amino acid sequence;   (ii) a first longer peptide which incorporates the sequence of a said peptide or a said modified peptide and which has up to four extra amino acid residues attached to the C-terminal end of the said sequence or up to four extra amino acid residues attached to the N-terminal end of said sequence or up to four extra amino acid residues attached to the C-terminal end and up to four extra amino acid residues attached to the N-terminal end of said sequence; or   (iii) a second longer peptide which incorporates the sequence of a said peptide, a said modified peptide or a said first longer peptide, to which sequence is linked directly, by means of a further amino acid residue or by means of a disulphide bridge between Cys residues attached to each sequence, a sequence of up to eighteen amino acid residues which comprises a hexapeptide sequence coded for by codons 93 to 98 in said RNA sequence or by equivalent codons of another poliovirus;   each said antigenic equivalent being capable of raising antibodies capable of neutralizing the same strain and type of poliovirus as said peptide to which said antigenic equivalent corresponds and the numbers of the codons being counted being the 5'-terminus of the nucleotide sequence coding for the VP1 capsid protein.